Balance Of Bone Metabolism Research Articles

Herbal formula xuling-jiangu improves bone metabolic balance in rats with ovariectomy-induced osteoporosis via the gut-bone axis.

The XuLing JianGu recipe (XLJGR) is an empirical traditional Chinese medicine formula used for the treatment of osteoporosis. This study aims to explore the effects of XLJGR on the intestinal microbiota composition and endogenous metabolites in ovariectomized (OVX) rats. An OVX rat model was established to evaluate the intervention effects of XLJGR. The measured indicators included bone density, serum bone metabolism markers, and an analysis of the types and abundances of intestinal microbiota, along with changes in endogenous metabolites. Additionally, MC3T3-E1 cells were used to validate the differential metabolites. XLJGR significantly reduced the abundance of Bacteroides, Butyricicoccus, and other bacterial strains in the gut. KEGG metabolic pathway enrichment analysis showed that XLJGR intervention led to notable changes in pathways such as peptidoglycan biosynthesis, carbapenem biosynthesis, and vancomycin resistance. Moreover, XLJGR significantly upregulated key intestinal microbiota metabolites, including gabapentin(GAB), camphoric acid(CAA), and nonanedioic acid(AZA), thereby promoting the proliferation and osteogenic differentiation of MC3T3-E1 cells. This study highlights the potential biomedical applications of XLJGR in promoting bone health by positively affecting intestinal microbiota and metabolic characteristics. These findings suggest that XLJGR may serve as a viable alternative in the treatment of osteoporosis, warranting further exploration of its therapeutic mechanisms and clinical applications.

Associations of oxidative balance score with lumbar spine osteopenia in 20-40 years adults: NHANES 2011-2018.

Current research suggests that oxidative stress may decrease bone mineral density (BMD) by disrupting bone metabolism balance. However, no study investigated the relationship between systemic oxidative stress status and adult BMD. This study aims to investigate whether oxidative balance score (OBS) is associated with BMD in adults under 40. 3963 participants were selected from the National Health and Nutrition Survey (NHANES) from 2011 to 2018. OBS is scored based on 20 dietary and lifestyle factors. Weighted multiple logistic regression and restricted cubic splines were used to assess the correlation between OBS and osteopenia. After adjusting for confounding factors, the weighted logistic regression results showed that compared with the first tertile of OBS, the highest tertile had a 38% (OR: 0.62, 95% CI: 0.47-0.82) lower risk of osteopenia. The restrictive cubic spline curve indicates a significant nonlinear correlation between OBS and the risk of osteopenia. The research findings emphasize the relationship between OBS and the risk of osteopenia in young adults. Adopting an antioxidant diet and lifestyle may help young adults to maintain bone mass.

Structural difference analysis of gut microbiota in different bone mass populations and relevant probiotic (lactobacilli) supplementation strategies

AbstractDisruption of the bone metabolic balance with advancing age leads to an escalating prevalence of bone‐related diseases, significantly compromising individuals’ quality of life. The gut microbiota actively participates in the regulation of bone metabolism, and perturbations in the gut microbiota can exacerbate bone diseases by compromising gut barrier integrity. Determining the microbial taxa involved in bone loss could offer valuable insights into the development of alternative therapies and nutritional interventions for disease management. Therefore, based on metagenomic and 16S ribosomal RNA data, this study analyzed the gut microbiota structure of 488 individuals with different bone masses (NC, normal; ON, osteopenia; OP, osteoporosis) to identify significant associations between the gut microbiota and bone loss. The results showed that at the genus and species levels, the microbiota diversity of the ON population increased, whereas that of the OP population decreased. Bacteroides were significantly enriched in the OP population, whereas the beneficial bacteria Bifidobacterium, Akkermansia, and lactobacilli decreased. Subsequent analyses revealed no significant variation in different bone populations in terms of Bifidobacterium levels, whereas lactobacilli exhibited diverse responses across distinct bone populations. The administration of lactobacilli effectively enhanced lumbar spine bone mineral density and modulated the gut microbiota structure in a population with unhealthy bone mass. This study contributes to the validation of the association between the gut microbiota and bone mass, enhances our understanding of the potential impact of probiotics (lactobacilli) on bone mass, and establishes a robust scientific basis for the application of probiotics in the regulation of bone mass.

3D-printed bone regeneration scaffolds modulate bone metabolic homeostasis through vascularization for osteoporotic bone defects

The treatment of osteoporotic bone defects poses a challenge due to the degradation of the skeletal vascular system and the disruption of local bone metabolism within the osteoporotic microenvironment. However, it is feasible to modulate the disrupted local bone metabolism imbalance through enhanced vascularization, a theory termed "vascularization-bone metabolic balance". This study developed a 3D-printed polycaprolactone (PCL) scaffold modified with EPLQLKM and SVVYGLR peptides (PCL-SE). The EPLQLKM peptide attracts bone marrow-derived mesenchymal stem cells (BMSCs), while the SVVYGLR peptide enhances endothelial progenitor cells (EPCs) vascular differentiation, thus regulating bone metabolism and fostering bone regeneration through the paracrine effects of EPCs. Further mechanistic research demonstrated that PCL-SE promoted the vascularization of EPCs, activating the Notch signaling pathway in BMSCs, leading to the upregulation of osteogenesis-related genes and the downregulation of osteoclast-related genes, thereby restoring bone metabolic balance. Furthermore, PCL-SE facilitated the differentiation of EPCs into "H"-type vessels and the recruitment of BMSCs to synergistically enhance osteogenesis, resulting in the regeneration of normal microvessels and bone tissues in cases of femoral condylar bone defects in osteoporotic SD rats. This study suggests that PCL-SE supports in-situ vascularization, remodels bone metabolic translational balance, and offers a promising therapeutic regimen for osteoporotic bone defects.

RNA sequencing-based approaches to identifying disulfidptosis-related diagnostic clusters and immune landscapes in osteoporosis.

Disulfidptosis, a newly recognized cell death triggered by disulfide stress, has garnered attention for its potential role in osteoporosis (OP) pathogenesis. Although sulfide-related proteins are reported to regulate the balance of bone metabolism in OP, the precise involvement of disulfidptosis regulators remains elusive. Herein, leveraging the GSE56815 dataset, we conducted an analysis to delineate disulfidptosis-associated diagnostic clusters and immune landscapes in OP. Subsequently, vertebral bone tissues obtained from OP patients and controls were subjected to RNA sequencing (RNA-seq) for the validation of key disulfidptosis gene expression. Our analysis unveiled seven significant disulfidptosis regulators, including FLNA, ACTB, PRDX1, SLC7A11, NUBPL, OXSM, and RAC1, distinguishing OP samples from controls. Furthermore, employing a random forest model, we identified four diagnostic disulfidptosis regulators including FLNA, SLC7A11, NUBPL, and RAC1 potentially predictive of OP risk. A nomogram model integrating these four regulators was constructed and validated using the GSE35956 dataset, demonstrating promising utility in clinical decision-making, as affirmed by decision curve analysis. Subsequent consensus clustering analysis stratified OP samples into two different disulfidptosis subgroups (clusters A and B) using significant disulfidptosis regulators, with cluster B exhibiting higher disulfidptosis scores and implicating monocyte immunity, closely linked to osteoclastogenesis. Notably, RNA-seq analysis corroborated the expression patterns of two disulfidptosis modulators, PRDX1 and OXSM, consistent with bioinformatics predictions. Collectively, our study sheds light on disulfidptosis patterns, offering potential markers and immunotherapeutic avenues for future OP management.

Long-term second-generation antipsychotics decreases bone formation and resorption in male patients with schizophrenia.

Patients with schizophrenia with second-generation antipsychotics (SGAs) treatment have shown an increased risk of bone fragility and susceptibility to fracture; however, it is still unclear whether this risk is derived from the effect of antipsychotics on balance of bone metabolism. We investigated the changes of two bone turnover biomarkers (BTMs) concentrations in people with schizophrenia receiving SGAs: procollagen type I aminoterminal propeptide (PINP) and C-terminal telopeptide of type I collagen (CTX-1) as BTMs of osteogenesis and bone resorption, respectively, to explore how antipsychotics contribute to bone fragility. We recruited 59 Chinese male patients with schizophrenia (32 drug-naïve first-episode (DNFE) patients and 27 chronic patients) to undergo 8 weeks SGAs treatment. Fasting peripheral blood samples of pre- and posttreatment were collected, plasma levels of PINP and CTX-1 were measured. The interaction effects of group and time on PINP and CTX-1 concentrations were found (P = .016 and P = .008). There was a significant decrease for both BTMs concentrations of the posttreatment compared to the pretreatment (P<.001 and P = .003). Chronic patients had significantly higher changes of BTMs concentrations compared to DNFE patients (P = .048 and P = .024). There was a positive correlation of the two BTMs of pretreatment with disease course in DNFE group (r = .37, P = .039;r = .38, P = .035) and a negative correlation of PINP of pretreatment with age in the chronic group (r=-.40, P = .039). Long-term SGAs medication inhibited osteogenesis in a dose- and time-dependent manner and damaged the balance of bone formation and bone resorption.

Impacts of immune microenvironment on musculoskeletal health

AbstractUnderstanding the interplay between immune cells and the bone marrow microenvironment is crucial for elucidating age‐related musculoskeletal changes. In this commentary manuscript, we summarized that studies have shown that proinflammatory immune cells in the bone marrow, such as macrophages and neutrophils, can inhibit bone formation by secreting grancalcin. Research on skeletal stem cells (SSCs) in aged mice reveals a shift towards pro‐inflammatory gene expression, affecting their osteogenic potential, while another study maps age‐related changes in cranial SSC niches, emphasizing the role of the CXCL12–CXCR4 axis in stem cell‐immune cell communication, Additionally, the immune system influences hematopoietic stem cells (HSCs); Niche ageing and accumulation of mutations with age lead to HSC exhaustion and a bias towards myeloid differentiation, with toll‐like receptors playing a key role in maintaining hematopoiesis and bone metabolism balance.

Erythropoietin receptor signal is crucial for periodontal ligament stem cell-based tissue reconstruction in periodontal disease

Alveolar bone loss caused by periodontal disease eventually leads to tooth loss. Periodontal ligament stem cells (PDLSCs) are the tissue-specific cells for maintaining and repairing the periodontal ligament, cementum, and alveolar bone. Here, we investigated the role of erythropoietin receptor (EPOR), which regulates the microenvironment-modulating function of mesenchymal stem cells, in PDLSC-based periodontal therapy. We isolated PDLSCs from patients with chronic periodontal disease and healthy donors, referred to as PD-PDLSCs and Cont-PDLSCs, respectively. PD-PDLSCs exhibited reduced potency of periodontal tissue regeneration and lower expression of EPOR compared to Cont-PDLSCs. EPOR-silencing suppressed the potency of Cont-PDLSCs mimicking PD-PDLSCs, whereas EPO-mediated EPOR activation rejuvenated the reduced potency of PD-PDLSCs. Furthermore, we locally transplanted EPOR-silenced and EPOR-activated PDLSCs into the gingiva around the teeth of ligament-induced periodontitis model mice and demonstrated that EPOR in PDLSCs participated in the regeneration of the periodontal ligament, cementum, and alveolar bone in the ligated teeth. The EPOR-mediated paracrine function of PDLSCs maintains periodontal immune suppression and bone metabolic balance via osteoclasts and osteoblasts in the periodontitis model mice. Taken together, these results suggest that EPOR signaling is crucial for PDLSC-based periodontal regeneration and paves the way for the development of novel options for periodontal therapy.

The Potential of Exosomes for Osteoporosis Treatment: A Review.

As a continuous process comprising bone resorption and formation, bone remodeling, plays an essential role in maintaining the balance of bone metabolism. One type of metabolic osteopathy is osteoporosis, which is defined by low bone mass and deteriorating bone microstructure. Osteoporosis patients are more likely to experience frequent osteoporotic fractures, which makes osteoporosis prevention and treatment crucial. A growing body of research has revealed that exosomes, which are homogenous vesicles released by most cell types, play a major role in mediating a number of pathophysiological processes, including osteoporosis. Exosomes may act as a mediator in cell-to-cell communication and offer a fresh perspective on information sharing. This review discusses the characteristics of exosomes and outlines the exosomes' underlying mechanism that contributes to the onset of osteoporosis. Recent years have seen a rise in interest in the role of exosomes in osteoporosis, which has given rise to innovative therapeutic approaches for the disease prevention and management.

Exploration of key factors in Gingival Crevicular fluids from patients undergoing Periodontally Accelerated Osteogenic Orthodontics (PAOO) using proteome analysis

BackgroundThe aims of this study are to explore protein changes in gingival crevicular fluid at different time points after PAOO by proteomics method and to select significant bone metabolization-related biomarkers.MethodsThis study included 10 adult patients experiencing PAOO. After orthodontic alignment and leveling, the maxillary anterior teeth were treated with PAOO, which is classified as the experimental area. The traditional orthodontic treatment was performed in the mandibular dentition as the control. Gingival crevicular fluid samples were collected at the following time points: the day before the PAOO (T1) and at 1 week, 2 weeks, 1 month, 2 months and 6 months after PAOO (T2, T3, T4, T5 and T6, respectively). The label-free quantitative proteomic assay was used to evaluate the gingival crevicular fluid in PAOO and control areas at time point T1, T2, and T4. Bioinformatics analysis was carried out to categorize proteins based on biological processes, cellular component and molecular function, which is in compliance with gene ontology (GO) standards. The changes of proteins were confirmed by ELISA.ResultsA total of 134 proteins were selected by keywords (Osteoblast markers, Osteoclast markers, Osteoclastogenesis regulating genes and inflammatory marker). 33 of them were statistically different between groups, and 12 were related to bone metabolism. 5 proteins selected by label-free quantitative proteomics were KLF10, SYT7, APOA1, FBN1 and NOTCH1. KLF10 decreased after PAOO, hitting a trough at T4, and then leveled off. SYT7 increased after PAOO, reaching a peak at T3, and then stabilized until T6. APOA1 ascended to a peak at T4 after PAOO, and then remained stable until T6. The FBN1 rose after PAOO, reaching a peak at T4, and then went down slowly. NOTCH1 ascended rapidly in the first two weeks after PAOO and continued its slow growth trend.ConclusionIn this study, protein changes in gingival crevicular fluid were detected by proteomics method, and significant bone metabolization-related proteins were selected. It is speculated that APOA1, FBN1, NOTCH1, SYT7 and KLF10 played key roles in regulating bone metabolic balance and in reversible osteopenia after PAOO, which might be involved in the accelerated tooth movement.Trial registrationThis study was registered in the Chinese Clinical Trial Registry (Clinical trial registration number: ChiCTR-ONRC-13,004,129) (26/04/2013).

Longbie capsules reduce bone loss in the subchondral bone of rats with comorbid osteoporosis and osteoarthritis by regulating metabolite alterations.

With the development of global population aging, comorbidity (≥2 diseases) is a common health problem among elderly people. Osteoarthritis (OA) and osteoporosis (OP) are common in elderly individuals. There is a lack of drug therapy for OA and OP comorbidities. The purpose of this study was to explore the efficacy and mechanism of Longbie capsule (LBJN), which contains various plant herbs, in treating OA and OP comorbidities (OA + OP) in rats using metabolomics techniques. We created an OA + OP rat model through bilateral oophorectomy combined with meniscus instability surgery. Thirty SD rats were randomly divided into five groups (six in each group), namely, the sham group, OA group, OA + OP group, LBJN low-dose group (0.625 g/kg, OA + OP+LB-L group) and LBJN high-dose group (1.25 g/kg, OA + OP+LB-H group). After 8 weeks of intervention, we used micro-CT to detect bone microstructure status, ELISA to measure bone metabolism indicators, and UPLC-MS technology for metabolomics analysis. Finally, the screened differentially expressed metabolites were subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and functional enrichment analysis. The micro-CT results showed that LBJN significantly improved the bone mineral density (BMD) and bone quality of subchondral bone in OA + OP rats, and LBJN regulated the expression of bone alkaline phosphatase (BALP), osteoprotegerin (OPG), and tartrate-resistant acid phosphatase (TRACP) in serum to maintain bone metabolism balance. Metabolomics analysis showed that the metabolic trajectory of OA + OP rats after intervention in the OA + OP+LB-H group showed significant changes, and 107 potential biomarkers could be identified. Among them, 50 metabolites were upregulated (such as zeranol) and 57 were downregulated (such as vanillactic acid). The KEGG functional enrichment results indicated that the differentially expressed metabolites are mainly involved in amino acid metabolism, lipid metabolism, and carbohydrate metabolism. The KEGG pathway enrichment results indicated that LBJN may exert therapeutic effects on OA + OP rats by regulating the cAMP signaling pathway, and the FoxO signaling pathway. LBJN can maintain bone metabolism balance by regulating serum lipid metabolism, amino acid metabolism, carbohydrate metabolism, and estrogen, thereby reducing bone loss in subchondral bone, which may be a potential mechanism through which LBJN treats OA + OP.

Screening diagnostic markers of osteoporosis based on ferroptosis of osteoblast and osteoclast.

Osteoporosis is a negative balance of bone metabolism caused by the lower bone formation of osteoblasts than the bone absorption of osteoclasts. Ferroptosis plays an important role in osteoporosis, but its effects on osteoblasts and osteoclasts are still unclear. First, we compared the osteogenic differentiation potential of MSCs and osteoclast differentiation potential of monocytes between osteoporosis mice and control. Then, we obtained gene expression profiles of MSCs and monocytes, and screened differentially expressed genes for enrichment analysis. Next, we cluster the patients with osteoporosis according to genes related to osteogenesis inhibition and osteoclast promotion. Finally, according to the expression of different subtypes of ferroptosis genes, diagnostic markers were screened and verified. The osteogenic differentiation ability of MSCs in osteoporosis mice was decreased, while the osteoclast differentiation ability of monocytes was enhanced. The DEGs of MSCs are enriched in iron ion, oxygen binding and cytokine activity, while the DEGs of monocytes are enriched in iron ion transmembrane transport and ferroptosis. Compared with the osteogenic inhibition subtype, the osteoclast promoting subtype has a higher correlation with ferroptosis, and its functions are enriched in fatty acids, reactive oxygen species metabolism and oxidoreductase activity of metal ions. SLC40A1 may be the hub gene of ferroptosis in osteoporosis by promoting osteoclast differentiation. Ferroptosis may inhibit bone formation and promote bone absorption through oxidative stress, thus leading to osteoporosis. The study of ferroptosis on osteoblasts and osteoclasts provides a new idea for the diagnosis and treatment of osteoporosis.

Bone and Soft Tissue Reaction to Co(II)/Cr(III) Ions Stimulation in a Murine Calvaria Model: A Pioneering in vivo Study.

Metal ions released during wear and corrosion of the artificial knee/hip joints are considered to contribute to aseptic implant failure. However, there are few convincing in vivo studies that demonstrate the effects of metal ions on bone and soft tissue. This study examined the in vivo effects of Co(II)/Cr(III) ions on mouse calvaria and the supra-calvaria soft tissue in an original mouse model. With the implantation of a helmet-like structure, we set up a subcutaneous cavity on the calvaria in which Co(II) Chloride or Cr(III) Chloride solutions were administered respectively. A layer of interface membrane formed on the calvaria along with the implantation of the helmet. The administered Cr(III) ions accumulated in the interface membranes while Co(II) disseminated into the circulation. Accumulated Cr(III) and related products induced local massive macrophage infiltration and skewed the bone metabolic balance. At last, we revealed that lymphocyte aggregates, which are the pathologic hallmark of human periprosthetic tissue, could be caused by either Co(II) or Cr(III) stimulation. These in vivo results may shed light on the effects and pathogenic mechanism of the Co(II)/Cr(III) ions released from the joint prosthesis. STATEMENT OF SIGNIFICANCE: Macrophage infiltration and lymphocyte aggregates are hallmarks of human joint periprosthetic tissue. We chronically administered Co(II)/Cr(III) ions on mouse calvaria and reproduced these two histopathologic hallmarks on mouse tissue based on an implanted helmet-like structure. Our results reveal that Cr(III) ions are locally accumulated and are effective in inducing macrophage infiltration and they can be phagocytosed and stored. However, the lymphocytes aggregates could be induced by both Co(II), Cr(III) and other unspecific inflammatory stimuli.

M2 macrophage-derived exosomes carry miR-142-3p to restore the differentiation balance of irradiatedBMMSCs by targeting TGF-β1.

Radiotherapy is essential to cancer treatment, while it inevitably injures surrounding normal tissues, and bone tissue is one of the most common sites prone to irradiation. Bone marrow mesenchymal stem cells (BMMSCs) are sensitive to irradiation and the irradiated dysfunction of BMMSCs may be closely related to irradiation-induced bone damage. Macropahges play important role in regulating stem cell function, bone metabolic balance and irradiation response, but the effects of macrophages on irradiated BMMSCs are still unclear. This study aimed to investigate the role of macrophages and macrophage-derived exosomes in restoring irradiated BMMSCs function. The effects of macrophage conditioned medium (CM) and macrophage-derived exosomes on osteogenic and fibrogenic differentiation capacities of irradiated BMMSCs were detected. The key microribonucleic acids (miRNAs) and targeted proteins in exosomes were also determined. The results showed that irradiation significantly inhibited the proliferation of BMMSCs, and caused differentiation imbalance of BMMSCs, with decreased osteogenic differentiation and increased fibrogenic differentiation. M2 macrophage-derived exosomes (M2D-exos) inhibited the fibrogenic differentiation and promoted the osteogenic differentiation of irradiated BMMSCs. We identified that miR-142-3p was significantly overexpressed in M2D-exos and irradiated BMMSCs treated with M2D-exos. After inhibition of miR-142-3p in M2 macrophage, the effects of M2D-exos on irradiated BMMSCs differentiation were eliminated. Furthermore, transforming growth factor beta 1 (TGF-β1), as a direct target of miR-142-3p, was significantly decreased in irradiated BMMSCs treated with M2D-exos. This study indicated that M2D-exos could carry miR-142-3p to restore the differentiation balance of irradiated BMMSCs by targeting TGF-β1. These findings pave a new way for promising and cell-free method to treat irradiation-induced bone damage.

Melatonin Promotes BMSCs Osteoblastic Differentiation and Relieves Inflammation by Suppressing the NF-κB Pathways.

Bone mesenchymal stem cells (BMSCs) play an important role in maintaining the dynamic balance of bone metabolism. Recent studies have reported that a decrease in the osteogenic function of MSCs is strongly associated with osteoporosis. Melatonin is a neuroendocrine hormone produced in the pineal gland and is essential in the physiological regulation. This study is aimed at exploring the effect of melatonin on MSCs osteoblastic differentiation and elucidate the underlying mechanisms. We isolated BMSCs from rat bone marrow and demonstrated that melatonin improved osteogenic differentiation of BMSCs by the alizarin red staining and ALP staining. We then showed that melatonin enhanced osteogenic gene expression in BMSCs, including ALP, Col 1, OCN, OPN, and RUNX2. We further revealed that melatonin inhibited the inflammatory response of BMSCs by suppressing the NF-κB signaling pathways. In light of this, we found that the NF-κB pathway-specific activator TNF-α activated the NF-κB pathway, inhibited osteogenic differentiation, and induced inflammatory response in BMSCs. Melatonin was found to reverse the inhibitory effect of TNF-α on osteogenic differentiation and inflammation in BMSCs. Taken together, these findings indicated that melatonin may have therapeutic potential to be used for the treatment of osteoporosis.

Research progress on the role and mechanism of miR-671 in bone metabolism and bone-related diseases.

Bone metabolism consists of bone formation and resorption and maintains a dynamic balance in vivo. When bone homeostasis is broken, it can manifest as osteoarthritis (OA), rheumatoid arthritis (RA), osteosarcoma (OS), etc. MiR-671, an important class of non-coding nucleotide sequences in vivo, is regulated by lncRNA and regulates bone metabolism balance by regulating downstream target proteins and activating various signaling pathways. Based on the structure and primary function of miR-671, this paper summarizes the effect and mechanism of miR-671 in bone-related inflammation and cancer diseases, and prospects the application possibility of miR-671, providing reference information for targeted therapy of bone-related disorders.

Asperosaponin VI Protects Against Bone Loss Due to Hindlimb Unloading in Skeletally Growing Mice Through Regulating Microbial Dysbiosis Altering the 5-HT Pathway.

Osteoporosis is a complex multifactorial disease that can lead to an increased risk of fracture. However, selective and effective osteoporosis drugs are still lacking. We showed that Asperosaponin VI (AVI) has the implications to be further developed as an alternative supplement for the prevention and treatment of bone loss. AVI has been found to have beneficial effects on metabolic diseases such as bone loss, obesity, and atherosclerosis. Our study was designed to determine the effect and mechanism of action of AVI against bone loss through regulating microbial dysbiosis. A hindlimb unloading mouse model was established to determine the effect of AVI on bone microarchitecture, gut microbiota, and serum metabolites. Eighteen female C57BL/6J mice were divided into three groups: control, hindlimb unloading with vehicle (HLU), and hindlimb unloading treated with AVI (HLU-AVI, 200mg/kg/day). AVI was administrated orally for 4weeks. The results demonstrated that AVI improved the bone microstructure by reversing the decrease in bone volume fraction and trabecular number, and the increase in trabecular separation and structure model index of cancellous bone in hindlimb suspension mice. The results of 16sRNA gene sequencing suggested that the therapeutic effect of AVI on bone loss may be achieved through it regulating the gut microbiota, especially certain specific microorganisms. Combined with the analysis of ELISA, immunohistochemistry, and serum metabolome results, it could be speculated that AVI played an important role in adjusting the balance of bone metabolism by influencing specific flora such as Clostridium and its metabolites to regulate the 5-hydroxytryptophan pathway. The study explored the novel mechanism of AVI against osteoporosis, and has implications for the further development of AVI as an alternative supplement for the prevention and treatment of bone loss.

The Role of Oxidative Stress in Multiple Exercise-Regulated Bone Homeostasis.

Bone is a tissue that is active throughout the lifespan, and its physiological activities, such as growth, development, absorption, and formation, are always ongoing. All types of stimulation that occur in sports play an important role in regulating the physiological activities of bone. Here, we track the latest research progress locally and abroad, summarize the recent, relevant research results, and systematically summarize the effects of different types of exercise on bone mass, bone strength and bone metabolism. We found that different types of exercise have different effects on bone health due to their unique technical characteristics. Oxidative stress is an important mechanism mediating the exercise regulation of bone homeostasis. Excessive high-intensity exercise does not benefit bone health but induces a high level of oxidative stress in the body, which has a negative impact on bone tissue. Regular moderate exercise can improve the body's antioxidant defense ability, inhibit an excessive oxidative stress response, promote the positive balance of bone metabolism, delay age-related bone loss and deterioration of bone microstructures and have a prevention and treatment effect on osteoporosis caused by many factors. Based on the above findings, we provide evidence for the role of exercise in the prevention and treatment of bone diseases. This study provides a systematic basis for clinicians and professionals to reasonably formulate exercise prescriptions and provides exercise guidance for patients and the general public. This study also provides a reference for follow-up research.

Influence of type 2 diabetes microangiopathy on bone mineral density and bone metabolism: A meta-analysis

BackgroundDiabetic microangiopathy is a type of vascular dysfunction. The effect of type 2 diabetes microangiopathy (DMA) on bone mineral density (BMD) and bone metabolism is still unclear. ObjectiveA meta-analysis was performed to investigate the effects of microangiopathy on BMD and bone metabolism in type 2 diabetic patients. MethodsWe searched the PubMed, Embase, Cochrane Library and CNKI databases to identify observational studies investigating the effects of type 2 diabetes microangiopathy on BMD or bone metabolism. The time limit for the literature retrieval was from the establishment of the database to September 25, 2021. The Newcastle–Ottawa scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) scale were used to evaluate the quality of the studies. RevMan 5.3 software was used for the data analysis. Stata 14.0 was used to quantitatively evaluate the publication bias of the outcome indicators. ResultsIn total, 12 observational studies were included, including 7 cohort studies, 4 case–control studies and 1 cross-sectional study. In total, 2,500 patients with type 2 diabetes were included. Among them, 1,249 patients had microangiopathy (DMA group), and 1,251 patients did not have microangiopathy (control group). The results of the meta-analysis showed that the BMDs of the femoral neck (SMD = −1.34, 95% CI = −2.22 to −0.45, P = 0.003), lumbar spine (SMD = −0.69, 95% CI = −1.31 to −0.08, P = 0.03) and Ward's triangle (SMD = −2.84, 95% CI = −4.84 to −0.83, P = 0.006) in the DMA group were lower than those in the control group. In the comparison of the bone metabolism indexes, the contents of N-terminal propeptide of type I procollagen (P1NP) (SMD = 0.18, 95% CI = 0.03 to 0.32, P = 0.02), osteocalcin (SMD = 6.97, 95% CI = 3.46 to 10.48, P < 0. 0001), parathyroid hormone (PTH) (SMD = 0.38, 95% CI = 0.03 to 0.73, P = 0.03) and C-telopeptide of type 1 collagen (CTX) (SMD = 0.39, 95% CI = 0.03 to 0.75, P = 0.03) in serum from the DMA group were higher than those in serum from the control group. The serum content of 25-hydroxyvitamin D3 (25(OH)D3) (SMD = −0.63, 95% CI = −1.19 to −0.07, P = 0.03) in the DMA group was lower than that in the control group. There was no significant difference in serum alkaline phosphatase (ALP), calcium or phosphorus between the two groups (P > 0.05). ConclusionsType 2 diabetes microangiopathy can reduce the lumbar spine, femoral neck and Ward's triangle BMD and has a higher risk of osteoporosis or osteoporosis fractures. The levels of P1NP, PTH, CTX and OC in the serum of patients with type 2 diabetes microangiopathy are higher, and the lower 25(OH)D3 content may be a mechanism by which DMA destroys bone metabolism balance.

Excessive fructose intake inhibits skeletal development in adolescent rats via gut microbiota and energy metabolism.

Excessive fructose intake from desserts and beverages may influence bone development among adolescents. The gut microbiota (GM) and energy metabolism play important roles in bone development. In this study, 40 female adolescent rats were randomly assigned to the control group, the fructose group with two concentrations, and the glucose group as the positive control group. After 10 weeks, serum glucose and lipids were detected by means of an automatic analyzer, and the bone microstructure was analyzed by Micro-CT. Then, the GM was determined via 16S rRNA sequencing analysis, and energy metabolism was detected by measuring serum carbohydrate metabolites. At last, bone metabolism markers were measured via ELISA kits. The results showed that excessive fructose intake could increase body weight and influence the glucolipid metabolism of female adolescent rats. Meanwhile, the bone microstructures were impaired with excessive fructose intake. Mechanistically, excessive fructose intake shifted the GM of rats with the decrease of Lachnospiraceae, Ruminococcaceae, and increase of Allobaculum, Lachnospiraceae. Energy metabolism analysis suggested that most metabolites of fructose did not enter the tricarboxylic acid cycle to provide energy for the body’s development. Furthermore, serum bone metabolism markers showed that excessive fructose intake could decrease both bone formation and resorption. Our results suggested that excessive fructose intake could inhibit skeletal development in adolescents. One potential mechanism might be that it affected the intestinal microbiota homeostasis in the juvenile body, thus changing the energy metabolism level, and ultimately affecting the bone metabolic balance.